Interested to have a link to the trials you are referring to Lyn as I read
Ga-PSMA ligand PET/CT shows substan-
tially higher detection rates than reported for other imaging mo-
dalities. Most importantly, it re
veals a high number of positive
findings in the clinically important range of low PSA values (
ng/mL), which in many cases can substantially influence the
further clinical management. Here is the link. https://www.snmmi.org/files/FileDownloads/J%20Nucl%20Med-2015-Eiber-668-74_1430513550878_2.pdf
Received: 25 March 2016
Accepted: 16 May 2016
Published: 8 June 2016
Recently, positron emission tomography (PET) imaging using PSMA-ligands has gained high attention as a promising new radiotracer in patients with prostate cancer (PC). Several studies promise accurate staging of primary prostate cancer and restaging after biochemical recurrence with 68Ga-PSMA ligand Positron emission tomography/computed tomography (PET/CT). However, prospective trials and clinical guidelines for this new technique are still missing. Therefore, we summarized our experience with 68Ga-PSMA ligand PET/CT examinations in patients with primary PC and biochemical recurrence. It focuses on the technical and logistical aspects of 68Ga-PSMA ligand PET/CT examination as well as on the specific background for image reading discussing also potential pitfalls. Further, it includes relevant issues on free-text as well as structured reporting used in daily clinical routine.
Prostate cancer Prostate specific membrane antigen Positron emission tomography
Prostate cancer (PC) represents the most common cancer in men and accounts for the third most cause for cancer-associated death in men . Early detection of primary disease and its metastases is highly relevant in terms of prognosis and therapy management. Primary staging with conventional imaging modalities such as computed tomography (CT) or magnetic resonance imaging (MRI) is limited as these techniques focus on morphologic information and LN involvement is mainly assessed by size. Up to 50 % of all patients undergoing radical prostatectomy (RP) or radiotherapy (RT) for primary treatment of PC develop biochemical recurrence [2, 3, 4]. Therefore, precise diagnosis of recurrence is crucial for patient counselling and treatment selection. However, the limited accuracy of CT or MRI in the detection of local disease in patients with biochemical recurrence is well appreciated [5, 6].
Positron emission tomography/computed tomography (PET/CT) as a hybrid imaging technique combining functional and morphological information has been proven to exhibit high diagnostic accuracy and is increasingly established as the primary staging tool in PC and in patients with suspicious recurrent disease. Several radiotracers have been proposed for molecular imaging of PC including choline as a marker of membrane cell proliferation. For recurrent PC, choline based (i.e. either 18F-Choline or 11C-Choline) PET/CT is currently widely used in clinical routine, however, there have been numerous studies reporting a low sensitivity and specificity [7, 8]. Especially in patients with prostate-specific antigen (PSA)-values below 3 ng/ml the detection rate is reported to be only 40–60 % [9, 10, 11].
Other radiotracers evaluated for PC include 11C-Acetate and 18F-FACBC. 18F fluciclovine, a radiolabeled leucine analog (1-amino-3-fluorocyclobutane-1-carboxylic acid in the ‘anti’ configuration [18F FACBC]), is used to depict amino acid transportation and has been found to be successful in the assessment of primary and metastatic PC showing also statistically significant superior detection rates in comparison to 11C-Choline PET [12, 13, 14]. 11C-Acetate is used as a PET radiotracer for imaging PC via incorporation into intracellular phosphatidylcholine membrane microdomains in cancer cells.
Current clinical and scientific evidence for 68Ga-PSMA ligand PET/CT and potential indications
The prostate specific membrane antigene (PSMA) is a transmembrane protein with significantly elevated expression in PC cells compared to benign prostatic tissue. So far, several, mainly retrospective studies describe the value of 68Ga-PSMA ligand PET/CT in different clinical scenarios. All of them demonstrate a higher diagnostic efficacy of 68Ga-PSMA ligand PET/CT compared to conventional imaging including PET with other tracers (e.g. 18F-Choline, 11C-Choline) [7, 15, 16, 17, 18, 19]. In particular, 68Ga-PSMA ligand PET/CT promises accurate staging of primary PC and re-staging after biochemical recurrence. In a large study in primary intermediate to high-risk PC, 68Ga-PSMA-ligand imaging has been reported to clearly improve detection of lymph node metastases compared to morphological imaging thus potentially allowing for a more tailored therapeutic concept .
Similar encouraging results were obtained for patients with biochemical recurrence after radical prostatectomy . Here, 68Ga-PSMA ligand PET imaging has been shown to increase detection of metastatic sites even at low PSA-values in comparison to conventional imaging or PET examination with different tracers . More specifically, in a study of Afshar-Oromieh et al. 68Ga-PSMA ligand PET/CT detected 78 lesions characteristic for recurrent PC in 32 patients while 18F-fluoromethylcholine PET/CT detected only 56 lesions in 26 patients resulting in a significant higher detection rate for 68Ga-PSMA ligand PET/CT . The advantage of 68Ga-PSMA ligand PET is especially evident in patients with low PSA levels (PSA below 1 ng/ml). A recent study reported a detection rate of 73 and 58 % in patients with biochemical recurrence after radical prostatectomy in a PSA-range of 0.5–1.0 ng/ml and 0.2–0.5 ng/ml, respectively . This facilitates the use of salvage procedures (e.g. secondary lymphadenectomy, targeted radiation therapy) with a potentially curative intent . Although 68Ga-PSMA ligand PET seems to have an edge over morphological imaging in patients with PC, the evaluation of PSMA-negative PC comprising around 8 % of the examined patients remains a challenge .
In nuclear medicine, bone imaging with 99mTc-phosphonates plays an important role in the management of PC patients according to current guidelines providing a fast whole-body overview evaluating the presence of bone metastases. Preliminary results from our department indicate that the detection rate of 68Ga-PSMA ligand PET/CT is clearly superior to traditional bone scan xaminations. It focuses on the technical and logistical issues as well as on the specific background for image reading with an emphasis on the PET-part since contrast enhanced computed tomography as the second part of a hybrid 68Ga-PSMA ligand PET/CT examination is an already very standardized and common imaging technique.
Synthesis, application and imaging protocol of 68Ga-PSMA ligand PET/CT
A number of different PSMA-targeted PET tracers have been developed [24, 25, 26, 27]. The most widely used PSMA-ligand for PET-imaging in Europe is a 68Ga-labelled PSMA inhibitor Glu-NH-CO-NH-Lys(Ahx)-HBED-CC (68Ga PSMA HBED-CC) followed by the theranostic agent 68Ga-labelled PSMA I&T [26, 27]. Details on the synthesis of 68Ga-labelled PSMA HBED-CC and 68Ga-labelled PSMA I&T have been described previously [27, 28]. Here is a link to the article https://cancerimagingjournal.biomedcentral.com/articles/10.1186/s40644-016-0072-6
The 68 Gallium PSMA scan developed in Heidelberg and shown to be superior to the Chlorine one is now available in other European countries and at UCLH in the UK. It may well be available at other UK hospitals by now.